C-reactive protein (CRP) is an independent predictor of cardiovascular disease (CVD) in men and women. CRP is a marker of systemic inflammation and therapeutic lowering of CRP was found to result in reduced CVD risk. CRP may have particular relevance as a CVD risk factor in post-menopausal women as cross-sectional and intervention studies find that hormone replacement therapy (HRT) substantially increases CRP. We have preliminary cross-sectional data suggesting that the HRT-CRP relation may be abolished by higher levels of cardiorespiratory fitness, independently of body mass index. The idea that cardiorespiratory fitness, a reflection of regular physical activity habits, may affect CRP presents an exciting potential mechanism to reduce CRP in postmenopausal women. To our knowledge there are no published reports from randomized clinical trials on the effect of exercise training alone on CRP in postmenopausal women, nor are there any studies examining the effects of different doses of exercise on changes in CRP. The proposed research consists of 2 studies and both will capitalize on ongoing NIH-funded projects at our center. The 1st is a cross-sectional epidemiological study from the NIA-funded Aerobics Center Longitudinal Study (AG06945). Our plan is to abstract additional data from the existing medical records to expand preliminary work exploring the relation between cardiorespiratory fitness, HRT use, and CRP levels. The 2nd proposed study is a prospective ancillary study to the NHLBI-funded, Dose-Response to Exercise in Women (DREW) study (HL66262). In DREW, 450 overweight, sedentary, postmenopausal women will be randomly assigned either to a no-exercise control group or to 1 of 3 exercise groups at 50, 100, and 150%, respectively, of the consensus public health recommendations for weekly physical activity (exercise). The study period is 6 months and all exercise sessions are supervised. We propose to measure CRP from frozen plasma samples to examine the dose-response relation between changes in physical activity (and fitness) and CRP. Additionally, we propose to measure visceral adiposity in a sub-set of the DREW participants to evaluate the relative importance of changes in body composition and fat distribution and changes in physical activity (and fitness) in relation to changes in CRP. These studies represent an innovative, unique, timely, and cost-effective opportunity to quickly explore the relation between CRP, physical activity, and HRT.